TY - JOUR
T1 - Protection against SARS-CoV-2 transmission by a parenteral prime-Intranasal boost vaccine strategy
AU - Christensen, Dennis
AU - Polacek, Charlotta
AU - Sheward, Daniel J
AU - Hanke, Leo
AU - Moliner-Morro, Ainhoa
AU - McInerney, Gerald
AU - Murrell, Ben
AU - Hartmann, Katrine Top
AU - Jensen, Henrik Elvang
AU - Jungersen, Gregers
AU - Illigen, Kristin
AU - Isling, Louise Krag
AU - Jensen, Rune Fledelius
AU - Hansen, Julia Sid
AU - Rosenkrands, Ida
AU - Fernandez-Antunez, Carlota
AU - Ramirez, Santseharay
AU - Follmann, Frank
AU - Bukh, Jens
AU - Pedersen, Gabriel Kristian
N1 - Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2022/10
Y1 - 2022/10
N2 - BACKGROUND: Licensed vaccines against SARS-CoV-2 effectively protect against severe disease, but display incomplete protection against virus transmission. Mucosal vaccines providing immune responses in the upper airways are one strategy to protect against transmission.METHODS: We administered Spike HexaPro trimer formulated in a cationic liposomal adjuvant as a parenteral (subcutaneous - s.c.) prime - intranasal boost regimen to elicit airway mucosal immune responses and evaluated this in a Syrian hamster model of virus transmission.FINDINGS: Parenteral prime - intranasal boost elicited high-magnitude serum neutralizing antibody responses and IgA responses in the upper respiratory tract. The vaccine strategy protected against virus in the lower airways and lung pathology, but virus could still be detected in the upper airways. Despite this, the parenteral prime - intranasal booster vaccine effectively protected against onward SARS-CoV-2 transmission.INTERPRETATION: This study suggests that parenteral-prime mucosal boost is an effective strategy for protecting against SARS-CoV-2 infection and highlights that protection against virus transmission may be obtained despite incomplete clearance of virus from the upper respiratory tract. It should be noted that protection against onward transmission was not compared to standard parenteral prime-boost, which should be a focus for future studies.FUNDING: This work was primarily supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.
AB - BACKGROUND: Licensed vaccines against SARS-CoV-2 effectively protect against severe disease, but display incomplete protection against virus transmission. Mucosal vaccines providing immune responses in the upper airways are one strategy to protect against transmission.METHODS: We administered Spike HexaPro trimer formulated in a cationic liposomal adjuvant as a parenteral (subcutaneous - s.c.) prime - intranasal boost regimen to elicit airway mucosal immune responses and evaluated this in a Syrian hamster model of virus transmission.FINDINGS: Parenteral prime - intranasal boost elicited high-magnitude serum neutralizing antibody responses and IgA responses in the upper respiratory tract. The vaccine strategy protected against virus in the lower airways and lung pathology, but virus could still be detected in the upper airways. Despite this, the parenteral prime - intranasal booster vaccine effectively protected against onward SARS-CoV-2 transmission.INTERPRETATION: This study suggests that parenteral-prime mucosal boost is an effective strategy for protecting against SARS-CoV-2 infection and highlights that protection against virus transmission may be obtained despite incomplete clearance of virus from the upper respiratory tract. It should be noted that protection against onward transmission was not compared to standard parenteral prime-boost, which should be a focus for future studies.FUNDING: This work was primarily supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.
KW - CAF®01
KW - Intranasal vaccine
KW - Neutralizing antibodies
KW - Onward transmission
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85139337981&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2022.104248
DO - 10.1016/j.ebiom.2022.104248
M3 - Journal article
C2 - 36088218
SN - 2352-3964
VL - 84
SP - 104248
JO - EBioMedicine
JF - EBioMedicine
M1 - 104248
ER -